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Journal

Anti�IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis

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Published:25th Mar 2020
Background: Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence. IL-5 is essential for eosinophil trafficking, and anti�IL-5 therapy decreases esophageal eosinophilia. EoE is associated with prominent mast cell infiltration. Objective: We investigated whether anti�IL-5 (mepolizumab) treatment reduced esophageal mast cell accumulation in biopsy specimens from pediatric patients with EoE from a previous randomized anti�IL-5 trial. Methods: A subanalysis was completed for children treated with 0.55, 2.5, or 10 mg/kg mepolizumab monthly for 12 weeks followed by no treatment until week 24. Quantitative immunochemistry was used to assess the numbers of eosinophils, tryptase-positive mast cells, IL-9+ cells, and mast cell�eosinophil couplets before and after treatment. Results: Forty-three biopsy specimens had adequate tissue for paired analysis. Forty percent of subjects responded to anti�IL-5 (defined as <15 eosinophils per high-power field [hpf] after mepolizumab therapy), and 77% of all subjects had decreased numbers of mast cells after anti�il-5. in responders epithelial mast cell numbers decreased from 62 to 19 per hpf (p>< .001), were significantly lower than in nonresponders after therapy (P < .05), and correlated with eosinophil numbers (r = 0.75, P < .0001). Mast cells and eosinophils were found in couplets before therapy, and these were significantly decreased only in responders after anti�IL-5 (P < .001). Esophageal eosinophils comprised the majority of cells that made the mast cell growth factor IL-9. IL-9+ cell numbers decreased from 102 to 71 per hpf (P < .001) after anti�IL-5. Conclusions: Pediatric patients with EoE had significantly fewer mast cells, IL-9+ cells, and mast cell�eosinophil couplets in the esophageal epithelium after anti�IL-5 therapy. Because eosinophils were one source of IL-9, they might support esophageal mastocytosis.

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